Cargando…
Functional impact of subunit composition and compensation on Drosophila melanogaster nicotinic receptors–targets of neonicotinoids
Neonicotinoid insecticides target insect nicotinic acetylcholine receptors (nAChRs) and their adverse effects on non-target insects are of serious concern. We recently found that cofactor TMX3 enables robust functional expression of insect nAChRs in Xenopus laevis oocytes and showed that neonicotino...
Autores principales: | , , , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2023
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9934367/ https://www.ncbi.nlm.nih.gov/pubmed/36795653 http://dx.doi.org/10.1371/journal.pgen.1010522 |
_version_ | 1784889869369081856 |
---|---|
author | Komori, Yuma Takayama, Koichi Okamoto, Naoki Kamiya, Masaki Koizumi, Wataru Ihara, Makoto Misawa, Daitaro Kamiya, Kotaro Yoshinari, Yuto Seike, Kazuki Kondo, Shu Tanimoto, Hiromu Niwa, Ryusuke Sattelle, David B. Matsuda, Kazuhiko |
author_facet | Komori, Yuma Takayama, Koichi Okamoto, Naoki Kamiya, Masaki Koizumi, Wataru Ihara, Makoto Misawa, Daitaro Kamiya, Kotaro Yoshinari, Yuto Seike, Kazuki Kondo, Shu Tanimoto, Hiromu Niwa, Ryusuke Sattelle, David B. Matsuda, Kazuhiko |
author_sort | Komori, Yuma |
collection | PubMed |
description | Neonicotinoid insecticides target insect nicotinic acetylcholine receptors (nAChRs) and their adverse effects on non-target insects are of serious concern. We recently found that cofactor TMX3 enables robust functional expression of insect nAChRs in Xenopus laevis oocytes and showed that neonicotinoids (imidacloprid, thiacloprid, and clothianidin) exhibited agonist actions on some nAChRs of the fruit fly (Drosophila melanogaster), honeybee (Apis mellifera) and bumblebee (Bombus terrestris) with more potent actions on the pollinator nAChRs. However, other subunits from the nAChR family remain to be explored. We show that the Dα3 subunit co-exists with Dα1, Dα2, Dβ1, and Dβ2 subunits in the same neurons of adult D. melanogaster, thereby expanding the possible nAChR subtypes in these cells alone from 4 to 12. The presence of Dα1 and Dα2 subunits reduced the affinity of imidacloprid, thiacloprid, and clothianidin for nAChRs expressed in Xenopus laevis oocytes, whereas the Dα3 subunit enhanced it. RNAi targeting Dα1, Dα2 or Dα3 in adults reduced expression of targeted subunits but commonly enhanced Dβ3 expression. Also, Dα1 RNAi enhanced Dα7 expression, Dα2 RNAi reduced Dα1, Dα6, and Dα7 expression and Dα3 RNAi reduced Dα1 expression while enhancing Dα2 expression, respectively. In most cases, RNAi treatment of either Dα1 or Dα2 reduced neonicotinoid toxicity in larvae, but Dα2 RNAi enhanced neonicotinoid sensitivity in adults reflecting the affinity-reducing effect of Dα2. Substituting each of Dα1, Dα2, and Dα3 subunits by Dα4 or Dβ3 subunit mostly increased neonicotinoid affinity and reduced efficacy. These results are important because they indicate that neonicotinoid actions involve the integrated activity of multiple nAChR subunit combinations and counsel caution in interpreting neonicotinoid actions simply in terms of toxicity. |
format | Online Article Text |
id | pubmed-9934367 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-99343672023-02-17 Functional impact of subunit composition and compensation on Drosophila melanogaster nicotinic receptors–targets of neonicotinoids Komori, Yuma Takayama, Koichi Okamoto, Naoki Kamiya, Masaki Koizumi, Wataru Ihara, Makoto Misawa, Daitaro Kamiya, Kotaro Yoshinari, Yuto Seike, Kazuki Kondo, Shu Tanimoto, Hiromu Niwa, Ryusuke Sattelle, David B. Matsuda, Kazuhiko PLoS Genet Research Article Neonicotinoid insecticides target insect nicotinic acetylcholine receptors (nAChRs) and their adverse effects on non-target insects are of serious concern. We recently found that cofactor TMX3 enables robust functional expression of insect nAChRs in Xenopus laevis oocytes and showed that neonicotinoids (imidacloprid, thiacloprid, and clothianidin) exhibited agonist actions on some nAChRs of the fruit fly (Drosophila melanogaster), honeybee (Apis mellifera) and bumblebee (Bombus terrestris) with more potent actions on the pollinator nAChRs. However, other subunits from the nAChR family remain to be explored. We show that the Dα3 subunit co-exists with Dα1, Dα2, Dβ1, and Dβ2 subunits in the same neurons of adult D. melanogaster, thereby expanding the possible nAChR subtypes in these cells alone from 4 to 12. The presence of Dα1 and Dα2 subunits reduced the affinity of imidacloprid, thiacloprid, and clothianidin for nAChRs expressed in Xenopus laevis oocytes, whereas the Dα3 subunit enhanced it. RNAi targeting Dα1, Dα2 or Dα3 in adults reduced expression of targeted subunits but commonly enhanced Dβ3 expression. Also, Dα1 RNAi enhanced Dα7 expression, Dα2 RNAi reduced Dα1, Dα6, and Dα7 expression and Dα3 RNAi reduced Dα1 expression while enhancing Dα2 expression, respectively. In most cases, RNAi treatment of either Dα1 or Dα2 reduced neonicotinoid toxicity in larvae, but Dα2 RNAi enhanced neonicotinoid sensitivity in adults reflecting the affinity-reducing effect of Dα2. Substituting each of Dα1, Dα2, and Dα3 subunits by Dα4 or Dβ3 subunit mostly increased neonicotinoid affinity and reduced efficacy. These results are important because they indicate that neonicotinoid actions involve the integrated activity of multiple nAChR subunit combinations and counsel caution in interpreting neonicotinoid actions simply in terms of toxicity. Public Library of Science 2023-02-16 /pmc/articles/PMC9934367/ /pubmed/36795653 http://dx.doi.org/10.1371/journal.pgen.1010522 Text en © 2023 Komori et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Komori, Yuma Takayama, Koichi Okamoto, Naoki Kamiya, Masaki Koizumi, Wataru Ihara, Makoto Misawa, Daitaro Kamiya, Kotaro Yoshinari, Yuto Seike, Kazuki Kondo, Shu Tanimoto, Hiromu Niwa, Ryusuke Sattelle, David B. Matsuda, Kazuhiko Functional impact of subunit composition and compensation on Drosophila melanogaster nicotinic receptors–targets of neonicotinoids |
title | Functional impact of subunit composition and compensation on Drosophila melanogaster nicotinic receptors–targets of neonicotinoids |
title_full | Functional impact of subunit composition and compensation on Drosophila melanogaster nicotinic receptors–targets of neonicotinoids |
title_fullStr | Functional impact of subunit composition and compensation on Drosophila melanogaster nicotinic receptors–targets of neonicotinoids |
title_full_unstemmed | Functional impact of subunit composition and compensation on Drosophila melanogaster nicotinic receptors–targets of neonicotinoids |
title_short | Functional impact of subunit composition and compensation on Drosophila melanogaster nicotinic receptors–targets of neonicotinoids |
title_sort | functional impact of subunit composition and compensation on drosophila melanogaster nicotinic receptors–targets of neonicotinoids |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9934367/ https://www.ncbi.nlm.nih.gov/pubmed/36795653 http://dx.doi.org/10.1371/journal.pgen.1010522 |
work_keys_str_mv | AT komoriyuma functionalimpactofsubunitcompositionandcompensationondrosophilamelanogasternicotinicreceptorstargetsofneonicotinoids AT takayamakoichi functionalimpactofsubunitcompositionandcompensationondrosophilamelanogasternicotinicreceptorstargetsofneonicotinoids AT okamotonaoki functionalimpactofsubunitcompositionandcompensationondrosophilamelanogasternicotinicreceptorstargetsofneonicotinoids AT kamiyamasaki functionalimpactofsubunitcompositionandcompensationondrosophilamelanogasternicotinicreceptorstargetsofneonicotinoids AT koizumiwataru functionalimpactofsubunitcompositionandcompensationondrosophilamelanogasternicotinicreceptorstargetsofneonicotinoids AT iharamakoto functionalimpactofsubunitcompositionandcompensationondrosophilamelanogasternicotinicreceptorstargetsofneonicotinoids AT misawadaitaro functionalimpactofsubunitcompositionandcompensationondrosophilamelanogasternicotinicreceptorstargetsofneonicotinoids AT kamiyakotaro functionalimpactofsubunitcompositionandcompensationondrosophilamelanogasternicotinicreceptorstargetsofneonicotinoids AT yoshinariyuto functionalimpactofsubunitcompositionandcompensationondrosophilamelanogasternicotinicreceptorstargetsofneonicotinoids AT seikekazuki functionalimpactofsubunitcompositionandcompensationondrosophilamelanogasternicotinicreceptorstargetsofneonicotinoids AT kondoshu functionalimpactofsubunitcompositionandcompensationondrosophilamelanogasternicotinicreceptorstargetsofneonicotinoids AT tanimotohiromu functionalimpactofsubunitcompositionandcompensationondrosophilamelanogasternicotinicreceptorstargetsofneonicotinoids AT niwaryusuke functionalimpactofsubunitcompositionandcompensationondrosophilamelanogasternicotinicreceptorstargetsofneonicotinoids AT sattelledavidb functionalimpactofsubunitcompositionandcompensationondrosophilamelanogasternicotinicreceptorstargetsofneonicotinoids AT matsudakazuhiko functionalimpactofsubunitcompositionandcompensationondrosophilamelanogasternicotinicreceptorstargetsofneonicotinoids |